Recent research in cystic fibrosis.

This review emphasizes some of the positive accomplishments of cystic fibrosis research, 
some of the puzzles and some of the recent developments that 
have promise. One of the major unresolved questions is the maintenance 
of this lethal gene at such a high frequency, perhaps because 
of a heterozygote advantage in the past, no longer operative at 
present. Nothing is known of the chromosomal localization of the trait; 
except that chromosomes are morphologically normal, that it is autosomal, not 
sex linked and that there is no correlation with blood groups 
or major HLA loci. One of the important achievements of the 
past many years is that we understand relatively well the pathogenesis 
of most clinical manifestations of CF. The as yet unknown inherited 
basic defect or metabolic error of CF gives rise to two 
main anomalies: the electrolyte defect in exocrine sweat glands and the 
'mucous secretion' abnormality. While the results of tissue culture studies often 
have been conflicting and disparate, it does seem to be the 
consensus that the fibroblasts are affected by the basic metabolic error 
in some manner, and that they respond abnormally under different experimental 
circumstances. Virtually all investigators have found some anomalies in biologic fluids 
of CF, although using different approaches and methods. An abnormality in 
the function of the autonomic nervous system, which is so closely 
associated with the exocrine glands, has always been an attractive explanation 
for the generalized exocrinopathy of CF. The search for a genetic 
animal model for CF has led to interesting findings. 